Effect of Epidermal Growth Factor in Combination with Sucralfate or Omeprazole on the Healing of Chronic Gastric Ulcers in the Rat

Itoh, Makoto; Imai, Seiji; Joh, Takashi; Yokoyama, Yukio; Yasue, Naoji; Iwai, Akira; Matsusako, Kei; Endoh, Kazuo; Kawai, Takashi; Takeuchi, Toshihiko

doi:10.1097/00004836-199001001-00030

Cited by 20 publications

(7 citation statements)

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“…[100][101][102][103] We found that orally administered hEGF for 2 weeks significantly enhanced acetic acid ulcer healing in rats. 104) In addition, it was found that b-FGF also significantly enhanced ulcer healing (unpublished data).…”

Section: Growth Factors Epidermal Growth Factor (Egf)mentioning

confidence: 78%

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

208

166

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Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers Ͼ100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

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Section: Growth Factors Epidermal Growth Factor (Egf)mentioning

confidence: 78%

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

208

166

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“…Although the mechanisms leading to reduced concentration of luminal EGF during peptic ulcer healing are not yet defined, these data indicate that intragastric EGF has an important role in the control of mucosal repair and its decrease may predispose to the development of peptic ulcer. This view is further supported by studies showing that some antiulcer drugs, such as sucralfate and colloidal bismuth subcitrate, may bind and concentrate EGF in the ulcer bed (Konturek et al, 1988b;Nexø and Poulsen, 1987), while omeprazole may increase EGF concentration in the gastric juice possibly as a consequence of the inhibition of gastric acid secretion (Itoh et al, 1990). Sialoadenectomy decreases the antiulcer effect of colloidal bismuth subcitrate but its efficacy can be restored by oral administration of EGF.…”

Section: Epidermal Growth Factor and Transforming Growth Factor-alphamentioning

confidence: 92%

Role of growth factors and their receptors in gastric ulcer healing

Milani

Calabrò

2001

Microscopy Res & Technique

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The repair of gastric ulcers requires the reconstitution of epithelial structures and the underlying connective tissue, including vessels and muscle layers. Several growth factors have been implicated in this process, since they are able to regulate important cell functions, such as cell proliferation, migration, differentiation, secretion, and degradation of extracellular matrix, all of which are essential during tissue healing. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF), and trefoil factors (TFFs) are mainly involved in the reconstitution of the epithelial structures. Platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) play a major role in the reconstitution of connective tissue, including vessels and smooth muscle cells, and provide the extracellular matrix substrate for cell migration and differentiation. The expression of these growth factors and their receptors is increased during ulcer healing and, in some cases, intracellular signaling related to receptor binding and transduction has been demonstrated. EGF, TGF-alpha and TFFs are normally present either in the gastric juice or in the mucosa, and may exert their effects immediately after damage, before newly synthesized EGF and TFFs are released from the ulcer margin. The inhibition of their effects by neutralizing antibodies may result in delayed ulcer healing, while the administration of recombinant or natural analogues may improve ulcer repair. In this review, we will summarize the basic molecular characteristics of some of these growth factors, and will discuss available evidence supporting their role in the ulcer repair process.

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“…However, several studies suggest that luminal EGF is capable of stimulating growth and repair, acting via the luminal surface, when administered to the damaged bowel of both rats [82,[90][91][92]146] and humans [129].…”

Section: Epidermal Growth Factormentioning

confidence: 99%

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

Gauthier

Pouliot

Maubois

2006

Lait

125

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-EGF, BTC, IGF-I, IGF-II, TGF-β1, TGF-β2, FGF1 and 2, and PDGF are the main growth factors present in bovine milk and colostrum. All of these growth factors are also found in human milk but at a lower concentration. The various compositional data reported in the literature vary greatly but it is evidenced that the day of lactation has the most important effect. Milk growth factors are characterized by a neutral to alkaline isoelectric point (pI) and a molecular mass between 6400 g·mol -1 and 30000 g·mol -1 . However, many of the growth factors are in a latent form, bound to high-molecular-mass proteins. Milk growth factors are resistant generally to pasteurization but disulfide reducing agents have been found to inactivate some species such as TGF-β's. The published data on bioavailability of milk growth factors are somewhat contradictory but it is generally accepted that they are resistant to gastric digestion and they can exert local and systemic effects on the gastrointestinal tract. Cation-exchange chromatography has been widely used for the extraction of milk growth factors because of the basic nature of these molecules. Membrane separations such as microfiltration (MF) have also been used successfully for the extraction of immunoglobulins and of some growth factors from colostrum, while ultrafiltration (UF) was successful only at separating IGF-I and IGF-II in whey. Milk growth factor extracts have been developed for various applications such as treatment of gastrointestinal disorders and skin diseases, wound healing, and induction of oral tolerance.

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Effect of Epidermal Growth Factor in Combination with Sucralfate or Omeprazole on the Healing of Chronic Gastric Ulcers in the Rat

Cited by 20 publications

References 0 publications

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Role of growth factors and their receptors in gastric ulcer healing

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

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Effect of Epidermal Growth Factor in Combination with Sucralfate or Omeprazole on the Healing of Chronic Gastric Ulcers in the Rat

Cited by 20 publications

References 0 publications

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

Role of growth factors and their receptors in gastric ulcer healing

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

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Product

Resources

About

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—